Gene expression profiling of progressive papillary noninvasive carcinomas of the urinary bladder
Gene expression profiling of progressive papillary noninvasive carcinomas of the urinary bladder
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DOI：
10.1158/1078-0432.ccr-05-0259
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发表时间：
2005-06-15
影响因子：
11.5
通讯作者：
Hartmann, A
中科院分区：
文献类型：
--
作者：
Wild, PJ;Herr, A;Hartmann, A
目的：本研究的目的是定义非侵袭性和侵袭性膀胱癌的基因表达谱，以确定潜在的治疗或筛选目标，在膀胱癌，并定义相关的遗传变化的肿瘤进展复发性乳头状膀胱癌（pTa）实验设计：总体而言，67膀胱肿瘤（46 pTa，3 pTis，10 pT1，和8 pT2）和8个正常膀胱标本进行了研究相结合的激光显微切割和基因表达谱。16例复发性非浸润性乳头状膀胱肿瘤患者中有8例在一段时间内发展为原位癌（pTis）或浸润性膀胱癌（>= pT1G2）。假定的进展标志物组织蛋白酶E（CTSE）的RNA表达结果通过使用高通量组织微阵列分析的免疫组织化学确认（n = 776）。单因素分析的因素，总生存期，无进展生存期，无复发生存的患者尿路上皮膀胱cancer.Results：分层聚类分析显示pTaG1和pTaG2肿瘤之间没有差异。然而，在乳头状瘤和实体瘤中发现了具有不同基因表达谱的不同浸润性癌症组。FABP4和CTSE），并且已经存在于先前的非侵袭性乳头状肿瘤中。CTSE表达（P = 0.003）和高Ki-67标记指数至少5%（P = 0.01）是唯一的因素，与无进展生存的pTa肿瘤在我们的基因表达approach.Conclusions：基因表达谱显示新的基因与潜在的临床实用性，以选择患者更有可能发展为侵袭性疾病。
Purpose:The aim of the present study was to define gene expression profiles of noninvasive and invasive bladder cancer, to identify potential therapeutic or screening targets in bladder cancer, and to define genetic changes relevant for tumor progression of recurrent papillary bladder cancer (pTa).Experimental Design: Overall, 67 bladder neoplasms (46 pTa, 3 pTis, 10 pT1, and 8 pT2) and eight normal bladder specimens were investigated by a combination of laser microdissection and gene expression profiling. Eight of 16 patients with recurrent noninvasive papillary bladder tumors developed carcinoma in situ (pTis) or invasive bladder cancer (>= pT1G2) in the course of time. RNA expression results of the putative progression marker cathepsin E (CTSE) were confirmed by immunohistochemistry using high-throughput tissue microarray analysis (n = 776). Univariate analysis of factors regarding overall survival, progression-free survival, and recurrence-free survival in patients with urothelial bladder cancer was done.Results: Hierarchical cluster analyses revealed no differences between pTaG1 and pTaG2 tumors. However, distinct groups of invasive cancers with different gene expression profiles in papillary and solid tumors were found. Progression-associated gene profiles could be defined (e.g., FABP4 and CTSE) and were already present in the preceding noninvasive papillary tumors. CTSE expression (P = 0.003) and a high Ki-67 labeling index of at least 5% (P = 0.01) were the only factors that correlated significantly with progression-free survival of pTa tumors in our gene expression approach.Conclusions: Gene expression profiling revealed novel genes with potential clinical utility to select patients that are more likely to develop aggressive disease.